Thyroid follicular cells have the unique ability to concentrate iodide, which is organified and utilized for the synthesis of thyroid hormones. Transport of iodide across the follicular cell membrane, in concert with inward movement of Na.sup.+ along its gradient, is an active process mediated by the tissue-specific sodium-iodide symporter (NIS).
A cDNA sequence for the rat NIS gene has been reported [Dai G., et al. (1996)] and the corresponding human cDNA sequence has been described [Smanik P., et al. (1996)]. The intronexon organization of the gene has also been reported recently [Smanik P., et al. (1997)].
A retention of the ability to concentrate iodide via the NIS in carcinoma cells derived from thyroid follicular cells provides an opportunity to destroy these cells with administered radioiodine. The efficacy of this approach relies upon adequate expression of functional NIS. Unfortunately, NIS expression in human thyroid carcinoma cells can be variable or absent, leaving some carcinomas untreatable by this approach. To understand the regulation of expression of the NIS gene in normal and malignant thyroid tissues, it is essential to understand regulation of transcription of this gene.
Smanik P., et al. (1996) describe cloning a cDNA encoding the hNIS protein and provide nucleotide sequence information for the coding region of this cDNA. A short (347 bp) untranslated region upstream of the translated region is also provided by these workers. Recently, Smanik P., et al. (1997) have described the exon-intron structure of the hNIS gene; however, this reference is unconcerned with the promoter region.
An extensive region upstream of the rat NIS gene has been described [Tong Q., et al., (1997), Biochem. Biophys. Res. Comm., 239:34-41]. However, this region is not appreciably homologous with the promoter of the human NIS gene (vide infra). The authors report that a 90 bp region of the active rat promoter has a 75% homology with the hNIS gene. In our studies, the minimal active region of the rat NIS promoter of these workers has no more than 60% homology with the corresponding region of the human NIS promoter. Significantly, no thyroid-specific activity is demonstrated for the promoter of these authors. Some DNA sequence information pertaining to the promoter for the rat sodium-iodide symporter gene has also been described elsewhere [Endo T., et al., (1997), Mol Endocrinol 11 (11):1747].
An elucidation of the factors affecting regulation of expression of the human sodium-iodide symporter gene is critical to an understanding of its effects on iodide concentration in normal thyroid and thyroid carcinomas. Identification of the active promoter for the hNIS gene is expected to provide further insights that can lead to the development of new therapies for thyroid carcinomas using radioiodine.